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Rational design of Gi-biased CB1 agonist with reduced side effects.

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Title: Rational design of Gi-biased CB1 agonist with reduced side effects.
Authors: Liao YY; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Che J; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Gao YT; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Xue J; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China., Li L; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Wu LL; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Hu JX; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Hu MT; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Xie L; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Zhang H; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China., Shen DD; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China., Dong Y; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China., Zang S; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China., Zhang N; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China., Wang H; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Zhejiang 310013, China., Zhang Y; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: zhang_yan@zju.edu.cn., Dong X; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: dongxw@zju.edu.cn., Li XM; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China. Electronic address: lixm@zju.edu.cn.
Source: Cell [Cell] 2026 May 28; Vol. 189 (11), pp. 3432-3443.e16. Date of Electronic Publication: 2026 Apr 13.
Publication Type: Journal Article
Journal Info: Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
Database: MEDLINE Ultimate
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  Data: Rational design of G<subscript>i</subscript>-biased CB1 agonist with reduced side effects.
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  Data: <searchLink fieldCode="AU" term="%22Liao+YY%22">Liao YY</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Che+J%22">Che J</searchLink>; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Gao+YT%22">Gao YT</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Xue+J%22">Xue J</searchLink>; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Li+L%22">Li L</searchLink>; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Wu+LL%22">Wu LL</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Hu+JX%22">Hu JX</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Hu+MT%22">Hu MT</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Xie+L%22">Xie L</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Zhang+H%22">Zhang H</searchLink>; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Shen+DD%22">Shen DD</searchLink>; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Dong+Y%22">Dong Y</searchLink>; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Zang+S%22">Zang S</searchLink>; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Zhang+N%22">Zhang N</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China.<br /><searchLink fieldCode="AU" term="%22Wang+H%22">Wang H</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Zhejiang 310013, China.<br /><searchLink fieldCode="AU" term="%22Zhang+Y%22">Zhang Y</searchLink>; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China; Department of Pathology of Sir Run Run Shaw Hospital, Department of Pharmacology and Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address: zhang_yan@zju.edu.cn.<br /><searchLink fieldCode="AU" term="%22Dong+X%22">Dong X</searchLink>; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: dongxw@zju.edu.cn.<br /><searchLink fieldCode="AU" term="%22Li+XM%22">Li XM</searchLink>; Department of Neurology and Department of Psychiatry of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Nanhu Brain-Computer Interface Institute, Hangzhou 311100, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Center of Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Liangzhu Laboratory, Zhejiang University, Hangzhou 310058, China. Electronic address: lixm@zju.edu.cn.
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  Data: <searchLink fieldCode="JN" term="%220413066%22">Cell</searchLink> [Cell] 2026 May 28; Vol. 189 (11), pp. 3432-3443.e16. <i>Date of Electronic Publication: </i>2026 Apr 13.
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